MMP-8, A Breast Cancer Bone Metastasis Suppressor Gene

摘要

In order to study the role of MMP-8 on inhibition of cancer growth and progression, we initiated our work to clone the human MMP-8 cDNA and express it in vitro. The MMP-8 cDNA with a V5 epitope tag was cloned downstream into the CMV promoter vector. The construct was verified by sequencing. But the expression level of MMP-8 was not detected by Western blot analysis. The molecular mechanisms of how TGF-BetaI mediates stimulation of invasion and formation of bone metastasis have yet to be completely determined. ATF-3 (activating transcription factor-3) was strongly stimulated and its level was sustained by TGF-BetaI in highly invasive and bone metastatic breast cancer cells. We have identified for the first time that cyclin Al and MMP-13 are ATF- 3 target genes. ATF-3 also regulates Runx2 (a bone specific transcription factor) in human breast cancer cells and that may provide a molecular phenotype for ATF-3 to regulate its target genes associated with bone metastasis.